Luminex-based pilot study identifies novel serum autoantibodies associated with disease activity in patients with lupus nephritis.

Abstract

Objective: To explore the associations of novel serum autoantibodies with disease activity and organ injuries in patients with lupus nephritis (LN).

Method: This study included 75 patients with active LN (5 class II, 37 class IV, and 33 class V). Indirect immunofluorescence was used to measure serum anti-dsDNA; ELISA was used to measure serum anti-PLA2R and anti-C1q, and the Luminex method was used to measure 58 novel serum autoantibodies, with a median fluorescence intensity (MFI)/threshold ≥ 1.5 as the antibody positivity cutoff.

Results: The positivity rates for 11 novel antibodies (anti-PLA2R, anti-P2RY11, anti-DEXI, anti-HARS, anti-TUBA1B, anti-KRT8, anti-TUBB, anti-NCL, anti-HSPB1, anti-AGRN, and anti-LGALS8) were highly associated with SLE activity and were inconsistent with those for anti-dsDNA and anti-C1q. Anti-TUBA1B and anti-AGRN positivity may independently influence LN with extrarenal organ involvement (OR = 6.73, 95% CI = 1.19 ~ 38.09; OR = 6.11, 95% CI = 1.32 ~ 28.25, respectively). The positivity rate for anti-PLA2R as detected by the Luminex platform was 40%, whereas the rate among those detected by ELISA was 12.7%. Twenty-one patients who achieved renal remission were retested, and the positivity rates of anti-PLA2R (42.9% vs. 9.5%, P = 0.014), anti-KRT8 (47.6% vs. 4.8%, P = 0.001), and anti-AGRN (38.1% vs. 4.8%, P = 0.008) also significantly decreased from baseline.

Conclusion: On the basis of Luminex technology, the present study revealed multiple novel autoantibodies related to SLE activity and organ injury, especially anti-PLA2R, anti-KRT8, and anti-AGRN, thereby providing novel serological markers for the assessment of activity in patients with LN. Anti-TUBA1B and anti-AGRN are strongly associated with extrarenal involvement. Key Points • The Luminex method is highly sensitive and high-throughput for detecting serum autoantibodies. • LN patients with anti-TUBA1B and anti-AGRN positivity are more likely to be complicated by extrarenal organ involvement. • Serum anti-PLA2R, anti-KRT8, and anti-AGRN reflect the activity of SLE and provide novel serological markers for the evaluation of LN patients negative for anti-dsDNA and anti-C1q.